ArticleHuman genetics2009
Modifier gene study of meconium ileus in cystic fibrosis: statistical considerations and gene mapping results.
Article in Human genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 54 citations in OpenAlex.
- Genetic Modifying Factors of Cystic Fibrosis Phenotype: A Challenge for Modern Medicine.Journal of clinical medicine · 2021Review
- The GENDULF algorithm: mining transcriptomics to uncover modifier genes for monogenic diseases.Molecular systems biology · 2020Article
- Clinical expression of cystic fibrosis in a large cohort of Italian siblings.BMC pulmonary medicine · 2018Article
- Kcnn4 is a modifier gene of intestinal cystic fibrosis preventing lethality in the Cftr-F508del mouse.Scientific reports · 2018Article
- Mouse models of SLC4-linked disorders of HCOAmerican journal of physiology. Cell physiology · 2018Review
- Noninvasive analysis of the sputum transcriptome discriminates clinical phenotypes of asthma.American journal of respiratory and critical care medicine · 2015Article
- Cystic fibrosis.Nature reviews. Disease primers · 2015Review
- Meconium ileus in cystic fibrosis is not linked to central repetitive region length variation in MUC1, MUC2, and MUC5AC.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2014Article
- Disease-modifying genes and monogenic disorders: experience in cystic fibrosis.The application of clinical genetics · 2014Review
- The divergence, actions, roles, and relatives of sodium-coupled bicarbonate transporters.Physiological reviews · 2013Review
- Correctors of ΔF508 CFTR restore global conformational maturation without thermally stabilizing the mutant protein.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- The influence of genetics on cystic fibrosis phenotypes.Cold Spring Harbor perspectives in medicine · 2012Article
- Article
- Meconium ileus caused by mutations in GUCY2C, encoding the CFTR-activating guanylate cyclase 2C.American journal of human genetics · 2012Article
- Cystic fibrosis newborn screening: distribution of blood immunoreactive trypsinogen concentrations in hypertrypsinemic neonates.JIMD reports · 2012Article
- Parent-of-origin effects of FAS and PDLIM1 in attention-deficit/hyperactivity disorder.Journal of psychiatry & neuroscience : JPN · 2012Article
- Variation in MSRA modifies risk of neonatal intestinal obstruction in cystic fibrosis.PLoS genetics · 2012Article
- Initial interrogation, confirmation and fine mapping of modifying genes: STAT3, IL1B and IFNGR1 determine cystic fibrosis disease manifestation.European journal of human genetics : EJHG · 2011Article
- New animal models of cystic fibrosis: what are they teaching us?Current opinion in pulmonary medicine · 2011Review
- Intestinal obstruction syndromes in cystic fibrosis: meconium ileus, distal intestinal obstruction syndrome, and constipation.Current gastroenterology reports · 2011Review
Corrections and comments
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Authors and funding
25 authors at 15 institutions in 9 countries.
Funding
Abstract
Cystic fibrosis (CF) is a monogenic disease due to mutations in the CFTR gene. Yet, variability in CF disease presentation is presumed to be affected by modifier genes, such as those recently demonstrated for the pulmonary aspect. Here, we conduct a modifier gene study for meconium ileus (MI), an intestinal obstruction that occurs in 16-20% of CF newborns, providing linkage and association results from large family and case-control samples. Linkage analysis of modifier traits is different than linkage analysis of primary traits on which a sample was ascertained. Here, we articulate a source of confounding unique to modifier gene studies and provide an example of how one might overcome the confounding in the context of linkage studies. Our linkage analysis provided evidence of a MI locus on chromosome 12p13.3, which was segregating in up to 80% of MI families with at least one affected offspring (HLOD = 2.9). Fine mapping of the 12p13.3 region in a large case-control sample of pancreatic insufficient Canadian CF patients with and without MI pointed to the involvement of ADIPOR2 in MI (p = 0.002). This marker was substantially out of Hardy-Weinberg equilibrium in the cases only, and provided evidence of a cohort effect. The association with rs9300298 in the ADIPOR2 gene at the 12p13.3 locus was replicated in an independent sample of CF families. A protective locus, using the phenotype of no-MI, mapped to 4q13.3 (HLOD = 3.19), with substantial heterogeneity. A candidate gene in the region, SLC4A4, provided preliminary evidence of association (p = 0.002), warranting further follow-up studies. Our linkage approach was used to direct our fine-mapping studies, which uncovered two potential modifier genes worthy of follow-up.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.